Diabetic neuropathy (DN) remains the most common complication of diabetes mellitus, affecting approximately 9.6 million Americans. As more drugs and other therapies become available to actually help treat DN, early identification of this disorder will be critical to slowing its progression. However, when DN is still in its earliest stages and only affecting small nerve fibers (including those subserving autonomic function, and pain and temperature sensation), the diagnosis of DN can be very difficult to confirm. Current methodologies for identification of early small fiber DN have several drawbacks including being insensitive, invasive or labor intensive to perform. Since impairment in foot thermoregulation can provide a sensitive index of distal autonomic dysfunction, in this proposal we introduce the technique of ambulatory foot temperature monitoring as a non-invasive method for the diagnosis of small fiber DN. This test is convenient and sufficiently cost-effective to consider for use as a screening tool for the diagnosis of DN. The goal of this exploratory grant is to determine the value of this technique by using it in 50 patients with early diabetic neuropathy and 50 age- and sex-matched patients with diabetes but no clinical evidence of neuropathy. In Specific Aim 1, different characteristics of the temperature profiles will be compared in order to identify those parameters which most effectively discriminate between diabetic patients with early DN and those without. Specific Aim 2 will evaluate which markers identified in Specific Aim 1 provide the most effective measures of disease severity. Ultimately, the results obtained in this work may justify the use of ambulatory foot temperature monitoring in DN clinical trials, both as a screening tool for early disease and as an outcome measure.